TOLERABILITY AND EFFICACY OF A SLOW-RELEASE INDOMETHACIN TABLET IN ANKYLOSING SPONDYLITIS

The efficacy and tolerability of a new formulation of slow-releaseindomethacin tablet was compared in a double-blind cross-overmanner with a conventional indomethacin capsule in 30 patientswith ankylosing spondylitis. Gastrointestinal side-effects anddizziness were less frequent during the slow-release tabletperiod than during the capsule period. KEY WORDS: Ankylosing spondylitis, Indomethacin, Tolerability, Slow-release tablet ^*This formulation of indomethacin is not available in the UK—Ed.     

ACTH versus prednisone and placebo in herpes zoster treatment

The effect of ACTH (Synacthen-depot®) versus prednisone and placebo in the treatment of herpes zoster (HZ) was studied in a controlled clinical trial comprising 60 consecutive patients. The treatment groups were comparable regarding sex, age and pre-entry symptom duration. The skin changes, patients' pain scores and the consumption of analgesics were monitored. Regarding objective symptoms and the development of postherpetic neuralgia there was no difference between the two treatment groups and placebo, while the ACTH group showed a decrease in pain score and consumption of analgesics during the first 4 days of the trial. Whether this finding will justify the application of ACTH in early HZ is arguable. Neither ACTH nor prednisone influenced the development of postherpetic neuralgia but this negative finding may be inaccurate due to the small number of patients in the three groups. Severe side-effects did not occur.     

Long-term photochemotherapy: histopathological and immunofluorescence observations in 243 patients

Skin biopsies of 243 patients treated with photochemotherapy (PUVA) for 1--4 years were examined histologically. Two hundred and six patients were examined retrospectively after total cumulative UV-A doses of 579 . 6 +/- 598 . 0 J/cm2 (mean +/- s.d.). An eosinophilic homogenization and a reduction of elastic fibres at the dermo--epidermal junction, and an increase of dermal macrophages were found as possible abnormalities. However, except for the increase of melanophages there was no statistically significant correlation between the incidence of these changes, the total UV-A dose applied and the skin type of the patients. Neither were such correlations found in thirty-seven patients biopsies twice after 394 . 8 +/- 267 . 6 J/cm2 and 808 . 5 +/- 458 . 9 J/cm2 (mean +/- s.d.), respectively. Studies with direct immunofluorescence techniques revealed no immunoglobulin deposits in PUVA treated skin in fifty-six patients after 469 . 2 +/- 370 . 2 J/cm2; antinuclear antibodies were observed in 4 . 6% of 129 patients after 169 J/cm2 (mean); in 11% of fifty-three patients reexamined after 381 J/cm2 (mean) and in 13 . 6% of twenty-two patients reexamined a second time after 643 J/cm2 (mean). Thirteen out of a total of 572 patients developed a peculiar mottling of skin in areas previously overdosed by PUVA. Subepidermal homogenization and reduction of elastic fibres were found in 45% of the patients, indicating that these changes indeed are a consequence of PUVA. Nuclear and cellular irregularities were found in 45% of the biopsies and 63% showed a disturbed epidermal architecture, but no carcinomas were observed. PUVA-induced mottling was reversible in 31%, partially reversible in 15%, but continued to be present in 54%.     

The Influence of Epitope Density on the Immunological Properties of Hapten-Protein Conjugates

The influence of epitope density on the induction of hapten-specific (B-cell) tolerance by dinitrophenytated bovine serum albumin (DNP.BSA) was investigated. Mice were given multiple iniections of DNP₅BSA or DNP₅₀BSA. and tolerance was assayed by challenge with DNP.haemocyanin Under 'conventional' tolerance-inducing conditions (5 mg three times a week for 2 to 8 weeks). anti-DNP anti body formation was completely suppressed by DNP₅₀BSA but only partially by DNP₅BSA. However, with a 2-week intensive regimen equal amounts of hapten as DNP₅BSA or as DNP₅₀BSA induced equal degrees of tolerance Since DNP₅₀BSA is lost from the body much more slowly than DNP₅BSA, these data suggest that high epitope density does not fundamentally affect the tolerogenicity of DNP.BSA. Partial tolerance preferentially suppressed IgG antibody formation to DNP.haemocyanin. whereas higher doses of DNP₅₀BSA produced complete DNP-specific tolerance. During spontaneous loss of tolerance the IgM response recovered more rapidly than the IgG response. These results strongly suggest that IgG precursor cells are more sensitive to tolerance induction than IgM precursors and that tolerance, once induced, is more profound in the former than in the latter.